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Quantitative comparison between the transplantability of human and murine tumors into the subcutaneous tissue of NCr/Sed-nu/nu nude and severe combined immunodeficient mice.

In previous reports, nude mice have demonstrated residual immunoreactivity against xenografts. Severe combined immunodeficient (SCID) mice lack functional T- and B-cells. These animals are expected to be better hosts in which to perform preclinical studies on human tumors. The purpose of this study is to quantitate the advantage of SCID mice over nude mice in terms of transplantability of human and murine tumors and the importance of residual immunity in SCID mice. The transplantation assays are described by an assay based on the number of tumor cells required to transplant tumor into 50% of recipients (TD50). Seven human tumors of different histology and four murine tumor cell lines were used. Serial 2-10-fold dilutions of cells were injected (0.1 ml) into the flanks of normal and whole-body irradiated WBI nude and SCID mice. The results showed that in 6 of 6 human tumor cell lines studied, TD50S for SCID mice were 2.4 to 200 times lower than that of nude mice (significant in 5 cell lines). In contrast, in 2 of 3 murine tumors, TD50S in WBI SCID mice were significantly higher than that found in nude mice. When SCID and nude mice received WBI, TD50S were lower than those of nonirradiated animals in 5 of 5 xenografts (significant in 2 cell lines for nude mice and in 5 cell lines for SCID mice). We concluded that WBI SCID mice are significantly better recipients of human tumor xenografts than nude mice. There is a factor of 10-1625 gain in TD50S in favor of the WBI SCID mice when compared to nonirradiated nude mice. WBI has, however, an important effect on SCID mice which may suggest a detectable residual immunoreactivity, perhaps due to natural killer cells. These data demonstrate that WBI SCID mice are better models for human tumor transplantation that nude mice and, although WBI at 6 Gy suppressed significantly the immune system of nude mice, a certain level of immunoreactivity against xenografts is still maintained.

Animals↗

Transcapillary forces of the subcutaneous tissue in patients treated with interleukin-2 and alpha-interferon: no capillary protein leak syndrome?

The purpose of this study was to evaluate whether treatment with interleukin-2 (IL-2) and alpha-interferon (IFN-alpha-2a) causes protein leakage from plasma to the interstitium, leading to the so called 'capillary leak syndrome'. This syndrome is supposed to cause dose-limiting side effects such as weight gain, edema and pleural effusions. Seven patients with disseminated malignant melanoma or renal carcinoma were studied before and after 5 and 12 days of treatment. Transcapillary forces were studied by measuring colloid osmotic pressures in plasma and interstitial fluid (on the thorax and ankle) with a 'wick' method. The colloid osmotic pressure in plasma was reduced by 30-35% during treatment, but with corresponding reductions in the interstitium. Hemoglobin, hematocrit, serum albumin and total protein decreased, whereas moderate edemas and weight gain were observed. These results demonstrate that during treatment with IL-2 and IFN-alpha-2a there are both fluid retention and augmented filtration of fluid from the vascular to the interstitial compartment, but no indication for a capillary leak syndrome. This may explain many of the cardiovascular side effects observed during such treatment.

Adult↗

Excision of subcutaneous tissue and deep muscle fascia for advanced lymphedema.

In advanced peripheral lymphedema particularly involving the legs, complex physical therapy (massage/bandage-wrapping compression, remedial exercises, and maintenance use of a low stretch elastic compression garment), is not uniformly successful. In six patients with morbid lymphedema of the legs, we described our positive experience using a modified Auchincloss/Homans excisional operation.

Adipose Tissue↗

Histochemistry of connective tissue cells in subcutaneous adipose tissue of normal and decapitated pig fetuses.

Connective tissue cells that are histochemically and morphologically distinct from 'fibroblasts' are localized around developing hair follicles in the pig and rat. Immature adipose tissue is limited to small areas immediately around fully descended hair follicles in the rat hypodermis. In the present study, connective tissue around large nerves and blood vessels in fetal pig subcutaneous tissue was examined for the presence of enzymes typical of adipocytes. Samples from decapitated pig fetuses were studied so that the effects of an altered hormonal profile could be examined. Samples of dorsal subcutaneous adipose tissue were obtained from fetuses at 65, 70, 85, 90, 110, and 112 days of gestation. Fetuses were decapitated in utero at 45 days of gestation, and adipose tissue samples were obtained from these fetuses at 110 days of gestation. A close spatial relationship was observed between the growth of large blood vessels and nerves and fat cell cluster development in the older (greater than 70 days) fetuses. Connective tissue cells that were contiguous with fat cell clusters were histochemically identical to adipocytes. The lipid histochemistry of the reactive connective tissue cells (histochemically identical to adipocytes) was variable in young fetuses. In all 110-and 112-day-old fetuses, the reactive cells contained lipid, whereas the reactive cells in decapitated fetuses were devoid of lipid. The reactive connective tissue cells were not associated with capillaries and did not contain basement membranes. The histochemistry of these cells suggests that they respond to a particular hormonal or metabolic profile as do adipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Does visceral adipose tissue differ from subcutaneous adipose tissue in fatty acid content?

OBJECTIVE: To determine whether intra-abdominal adipose tissue differs from subcutaneous adipose tissue in fatty acid content. DESIGN: Cross-sectional study of patients undergoing exploratory laparotomy, with adipose tissue sampling from subcutaneous, omental, mesenteric and retroperitoneal sites. SUBJECTS: Nineteen subjects, 8 men and 11 women, with a mean age of 64 (range 39-80), mean weight 78.9 kg (range 51-157) and mean body mass index of 27.5 (range 19.2-51.4). Fourteen of the 19 were undergoing surgery for colorectal cancer. MEASUREMENTS: Fatty acid content was assessed by gas chromatography and was compared between sites and between patients using general linear modeling. Spearman correlation coefficients were used to assess the association between subcutaneous and visceral adipose tissue. RESULTS: For each of 17 fatty acids analyzed, there was a statistically significant difference in mean fatty acid values across individuals (p < 0.001). For seven of the fatty acids, there was a borderline or significant difference in mean fatty acid values across site, but there was no consistent pattern for one site differing from the others. Subcutaneous adipose tissue fatty acid content was highly correlated to visceral adipose tissue for saturated, unsaturated and trans fatty acids (p < 0.05 for 13 of 17 fatty acids). Variability across individuals was much greater than across site. The total explained variability (R2) for each fatty acid ranged between 49 and 93%, with the vast majority contributed by differences between individuals. CONCLUSION. Fatty acid content of subcutaneous abdominal adipose tissue is a good approximation of visceral adipose tissue. Because variability in fatty acid content is much larger between individuals than within a single individual across sites, subcutaneous abdominal adipose tissue fatty acid content can be used as a distinguishing characteristic among human populations.

Adipose Tissue↗

Expression of resistin protein in normal human subcutaneous adipose tissue and pregnant women subcutaneous adipose tissue and placenta.

The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta and the relationship between obesity, type 2 diabetes mellitus (T2DM), pregnant physiological insulin resistance (IR) and gestational diabetes mellitus (GDM) was investigated. The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta was detected by using Western blotting method. Fasting serum glucose concentration was measured by glucose oxidase assay. Serum cholesterol (CHOL), serum triglycerides (TG), serum HDL cholesterol (HDL-C) and serum LDL cholesterol (LDL-C) were determined by full automatic biochemical instrument. Fasting insulin was measured by enzyme immunoassay to calculate insulin resistance index (IRI). Height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured to calculate body mass index (BMI) and body fat percentage (BF %). Resistin protein expression in pregnant women placental tissue (67 905 +/- 8441) (arbitrary A values) was much higher than that in subcutaneous adipose tissue in pregnant women abdomen (40 718 +/- 3818, P < 0.01), non-pregnant women abdomen (38 288 +/- 2084, P < 0.01), normal human abdomen (39 421 +/- 6087, P < 0.01) and thigh (14 942 +/- 6706, P < 0.001) respectively. The resistin expression in abdominal subcutaneous adipose tissue showed no significant difference among pregnant, non-pregnant women and normal human, but much higher than that in thigh subcutaneous adipose tissue (P < 0.001). Pearson analysis revealed that resistin protein was correlated with BMI (r = 0.42), fasting insulin concentration (r = 0.38), IRI (r = 0.34), BF % (r = 0.43) and fasting glucose (r = 0.39), but not with blood pressure, CHOL, TG, HDL-C and LDL-C. It was suggested that resistin protein expression in human abdominal subcutaneous adipose tissue was much higher than that in human thigh subcutaneous adipose tissue. Resistin was closely related with central obesity, leading to IR, subsequently obesity and T2DM. Resistin protein expression in placental tissue was much higher than that in subcutaneous adipose tissue in normal human abdomen, pregnant abdomen, non-pregnant women abdomen and thigh. It was indicated that resistin protein could be secreted from human placental tissue. Resistin might be one of the factors that lead to pregnant physiological IR and GDM.

Blood Glucose↗